U.S. patent application number 16/893296 was filed with the patent office on 2020-09-24 for reinforced orthopedic devices and methods.
This patent application is currently assigned to Tela Bio, Inc. The applicant listed for this patent is Tela Bio, Inc. Invention is credited to E. Skott GREENHALGH, Antony KOBLISH.
Application Number | 20200297476 16/893296 |
Document ID | / |
Family ID | 1000004870477 |
Filed Date | 2020-09-24 |
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United States Patent
Application |
20200297476 |
Kind Code |
A1 |
GREENHALGH; E. Skott ; et
al. |
September 24, 2020 |
REINFORCED ORTHOPEDIC DEVICES AND METHODS
Abstract
Implantable tensile load-bearing grafts having synthetic
components stitched through biological components are disclosed.
The synthetic components can be biodegradable and/or
non-biodegradable and of differing tensile strengths from each
other and the biological component. Methods of making the grafts
are also disclosed.
Inventors: |
GREENHALGH; E. Skott;
(Gladwyne, PA) ; KOBLISH; Antony; (Malvern,
PA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Tela Bio, Inc |
Malvern |
PA |
US |
|
|
Assignee: |
Tela Bio, Inc
Malvern
PA
|
Family ID: |
1000004870477 |
Appl. No.: |
16/893296 |
Filed: |
June 4, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
15272389 |
Sep 21, 2016 |
10675141 |
|
|
16893296 |
|
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62221602 |
Sep 21, 2015 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61F 2002/087 20130101;
A61F 2002/0858 20130101; A61F 2/08 20130101; A61F 2/0811
20130101 |
International
Class: |
A61F 2/08 20060101
A61F002/08 |
Claims
1. An implantable orthopedic device for implantation as a tensile
load bearing element in a target site comprising: a biological
component comprising a soft tissue and a hard tissue; a first
synthetic component configured to sustain a first portion of a
tensile load; and a second synthetic component configured to
sustain a second portion of the tensile load, wherein the second
synthetic component extends through the biological component such
that the second synthetic component extends out of a first hard
tissue channel through the hard tissue into a soft tissue channel
through the soft tissue and into a second hard tissue channel
through the hard tissue, and wherein the first hard tissue channel
and the second hard tissue channel are in the same piece of hard
tissue.
2. The device of claim 1, wherein the second synthetic component
extends through the soft tissue and the hard tissue such that the
second synthetic component sequentially extends from the hard
tissue, into the soft tissue, and then back into the hard
tissue.
3. The device of claim 1, wherein the second synthetic component is
stitched through the soft tissue and the hard tissue.
4. The device of claim 1, wherein a total length of the first
synthetic component is greater than a total length of the soft
tissue.
5. The device of claim 1, wherein a total length of the first
synthetic component is greater than a total length of the hard
tissue.
6. The device of claim 1, wherein a total length of the first
synthetic component is greater than a total length of the
biological component.
7. The device of claim 1, wherein the second synthetic component
overlaps with the first synthetic component.
8. The device of claim 1, wherein the soft tissue comprises at
least one of a ligament, a tendon, and a muscle.
9. The device of claim 1, wherein the hard tissue comprises a first
bone plug at a first end of the device and a second bone plug at a
second end of the device.
10. An implantable orthopedic device for implantation as a tensile
load bearing element in a target site comprising: a biological
component comprising a soft tissue and a hard tissue; a first
synthetic component configured to sustain a first portion of a
tensile load; and a second synthetic component configured to
sustain a second portion of the tensile load, wherein the second
synthetic component extends through hard tissue channels and
through soft tissue channels, wherein the hard tissue channels and
the soft tissue channels extend longitudinally from a biological
component first longitudinal end toward a biological component
second longitudinal end.
11. The device of claim 10, wherein the soft tissue channels are
closer to a longitudinal center of the biological component than
the hard tissue channels.
12. The device of claim 10, wherein the first synthetic component
overlaps with the second synthetic component in the soft
tissue.
13. The device of claim 10, wherein the first synthetic component
overlaps with the soft tissue channels.
14. The device of claim 10, wherein a length of the second
synthetic component is greater than a length of the soft
tissue.
15. The device of claim 10, wherein a length of the second
synthetic component is greater than a length of the hard tissue,
and wherein the length of the second synthetic component is greater
than a length of the soft tissue.
16. An implantable orthopedic device for implantation as a tensile
load bearing element in a target site comprising: a biological
component comprising a soft tissue and a hard tissue; a first
synthetic component configured to sustain a first portion of a
tensile load; and a second synthetic component configured to
sustain a second portion of the tensile load, wherein the second
synthetic component extends in multiple directions while following
a shape formed through a biological component channel that extends
in multiple directions through the soft tissue and through the hard
tissue.
17. The device of claim 16, wherein the biological component
channel extends in multiple directions back and forth from a
biological component first lateral side to a biological component
second lateral side along a biological component longitudinal
axis.
18. The device of claim 16, wherein the biological component
channel comprises a biological component first channel and a
biological component second channel, wherein the biological
component first channel comprises a hard tissue first channel and a
soft tissue first channel, wherein the biological component second
channel comprises a hard tissue second channel and a soft tissue
second channel, wherein the hard tissue first and second channels
are farther from a longitudinal center of the biological component
than the soft tissue first and second channels, and wherein the
hard tissue first channel is the same distance from the
longitudinal center of the biological component as the hard tissue
second channel.
19. The device of claim 18, wherein the hard tissue first channel
is aligned with the soft tissue first channel, wherein the hard
tissue second channel is aligned with the soft tissue second
channel, and wherein a length of the second synthetic component in
the hard tissue first channel is greater than a length of the hard
tissue.
20. The device of claim 18, wherein the hard tissue first channel
has multiple turns, and wherein the second synthetic component
extends along the multiple turns.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 15/272,389 filed Sep. 21, 2016, which claims
the benefit of priority to U.S. Provisional Application No.
62/221,602 filed Sep. 21, 2015, each of which is incorporated
herein by reference in its entirety for all purposes.
BACKGROUND
[0002] 1) Technical Field
[0003] This disclosure relates generally to implantable tensile
load-bearing grafts having synthetic components stitched through
biological components.
[0004] 2) Description of the Related Art
[0005] Reconstruction of a ruptured anterior cruciate ligament
(ACL) is one of the most common procedures performed by sports
medicine surgeons today. Few would dispute the importance of the
ACL to knee stability and function. Anatomic intra-articular
reconstruction is common for ACL patients or those with function
disability due to acute or chronic ACL deficiency.
[0006] However, some in the field previously stated that the ACL
did not need repair if the associated meniscal and capsular
pathology was appropriately addressed. They failed to recognize the
importance of the ACL as the primary restraint to anterior
translation of the tibia and the prevalence of isolated ACL
rupture.
[0007] Various techniques address the problem of ACL rupture.
Primary repair and substituting the ACL with extra-articular
reconstructions using local structures are known techniques but
considered outdated by many. A common repair procedure passes
grafts through a tibial tunnel and intra-articularly. The proximal
end of the graft is then passed through the condyle notch on the
femur and secured on the lateral aspect of the femur or through a
tunnel in the femur. Some procedures include a double-bundle:
implanting two grafts to attempt to mechanically replicate the
force loading of the ACL.
[0008] Soft-tissue grafts and synthetic prosthetic replacements are
used for ACL repair. Common tissue replacements include fascia lata
grafts, hamstring grafts, and quadriceps or patellar tendon (also
referred to as patellar ligament) grafts.
[0009] FIGS. 1a and 1b illustrate a variation of an ACL graft made
from patellar tendon. The graft has a tendon length in the middle
of the graft and bone plugs at each terminal end of the graft. The
bone can be integral with the tendon, having been the natural bone
at the ends of the tendon before excising the graft from the host
location, or can be attached to the tendon after the tendon is
removed from the host location. The graft is shown having a
generally rectangular cross-section, but circular cross-sectional
(i.e., cylindrical) grafts are also used.
[0010] Synthetic ACL replacements include structures made from
polyethylene, such as the Polyflex, porous PTFE (Teflon) grafts,
such as the Proplast, and grafts using carbon fiber, Gore-Tex,
Dacron, and polypropylene. The polypropylene graft known as the
Ligament Augmentation Device (LAD) was the only one to gain
widespread use. These synthetics often failed as they tended to
stretch or fragment over time.
[0011] Biological graft strength varies with time after implant.
Natural stressing of the graft is beneficial for long-term
strengthening of the graft, but the failure stress of biological
grafts decreases after implantation and before the strength of the
graft increases. Accordingly, failure of biological grafts may
occur during rigorous post-replacement physical therapy intended to
strengthen the graft. On the other hand, synthetic grafts start
strong after implantation, but are known to sometimes fail due to
long-term issues such as stretching or fragmentation.
[0012] Accordingly, it is desired to provide an ACL graft that has
the long-term strength and biocompatibility of a biological graft
with the short-term strength of a synthetic graft.
SUMMARY
[0013] An implantable orthopedic device, such as a graft, for
implantation as a tensile load bearing element in a target site is
disclosed. The device can have a biological component and a first
synthetic component. The biological component can have a
longitudinal axis. The biological component can be configured to
sustain a first portion of the tensile load. The biological
component can have a soft tissue and/or a hard tissue. The first
synthetic component can be configured to sustain a second portion
of the tensile load. The first synthetic component can extend
through the biological component. The first synthetic component may
not extend beyond the longitudinal extent of the biological
component.
[0014] At least a length of the first synthetic component can be
stitched through the biological component. At least a length of the
first synthetic component can form a lockstitch through the
biological component.
[0015] The device can have a second synthetic component configured
to sustain a third portion of the tensile load. The second
synthetic component can extend through the biological component.
The second synthetic element can overlap with the first synthetic
element in a longitudinal direction of the device. The second
synthetic component can have a non-biodegradable material. The
first synthetic component can have a biodegradable material.
[0016] The first synthetic component can have one or more yarns,
threads (e.g., multifilament or monofilament), fibers, leaders,
wires, cords, or combinations thereof. The soft tissue can have or
be a ligament, a tendon, a muscle, or combinations thereof. The
hard tissue can have or be a bone, a first bone plug at a first
terminal end of the device and a second bone plug at a second
terminal end of the device, or combinations thereof.
[0017] An implantable orthopedic device, such as a graft, for
implantation as a tensile load bearing element in a target site is
further disclosed. The device can have a biological component and a
first synthetic component. The biological component can have a
longitudinal axis and be configured to sustain a first portion of
the tensile load. The biological component can have a soft tissue
and/or a hard tissue.
[0018] The first synthetic component can be configured to sustain a
second portion of the tensile load. The first synthetic component
can extend through the biological component and be
biodegradable.
[0019] Furthermore, an implantable orthopedic device, such as a
graft, for implantation as a tensile load bearing element in a
target site is disclosed. The device can have a biological
component, a first synthetic component, and a second synthetic
component. The biological component can have a longitudinal axis
and be configured to sustain a first portion of the tensile load.
The biological component can have a soft tissue and/or a hard
tissue.
[0020] The first synthetic component can be configured to sustain a
second portion of the tensile load. The first synthetic component
can extend through the biological component. The first synthetic
material can have a first strength per cross-sectional area.
[0021] The second synthetic component can be configured to sustain
a third portion of the tensile load. The second synthetic component
can extend through the biological component. The second synthetic
material can have a second strength per cross-sectional area. The
second strength per cross-sectional area can be greater than the
first strength per cross-sectional area.
[0022] The first and second strength per cross-sectional area can
have or be a first and second modulus of elasticity, respectively.
The first and second strength per cross-sectional area can have or
be a first and second yield stress, respectively. The first and
second strength per cross-sectional area can have a first and
second failure stress, and wherein the second strength per
cross-sectional area comprises a second failure stress,
respectively.
[0023] A method for making an implantable orthopedic device is
disclosed. The method can include inserting a first synthetic
element through a biological component. The biological component
can have a soft tissue. The first synthetic element can be inserted
through the soft tissue. The first synthetic element can have a
first yarn. The method can further include inserting a second
synthetic element through the soft tissue. The second synthetic
element can be stronger than the first synthetic element.
[0024] The second synthetic element can overlap with the first
synthetic element in a longitudinal direction of the device. The
inserting of the first synthetic element can include forming a
lockstitch with the first synthetic element. The second synthetic
element can have a second yarn.
[0025] The method can include folding the biological component over
onto itself. The folding can include forming a pocket within the
biological component. The method can include placing an attachment
element in the pocket.
[0026] The method can include creating a bone tunnel, and attaching
an anchor to the attachment element. The anchor can have an
endobutton outside of the bone tunnel.
[0027] The method can include folding the biological component over
onto itself at a fold and attaching a bone plug to the fold.
[0028] Yet another method for making an implantable orthopedic
device is disclosed. The method can include inserting a first
synthetic element through a biological component having soft
tissue. The first synthetic element can be inserted through the
soft tissue. The first synthetic element can have a first yarn. The
method can include forming with and/or attaching an interference
element to the biological component. The method can include
attaching a bone plug to the soft tissue. The bone plug can abut
the interference element.
[0029] The method can include inserting a second synthetic element
through the bone plug and the soft tissue. The second synthetic
element can be stronger than the first synthetic element.
[0030] The interference element can have an interference bump
attached to the soft tissue. The interference element can have a
fold of the soft tissue.
[0031] An implantable orthopedic device is disclosed that can have
a bone plug, a first yarn; and a second yarn. The first yarn can be
stitched through the bone plug in a first stitching orientation.
The second yarn can be stitched through the bone plug in a second
stitching orientation. The first stitching orientation can be
non-parallel to the second stitching orientation. The device can
have a soft tissue attached to the bone plug. The first stitching
orientation can be at a right angle to the second stitching
orientation.
BRIEF DESCRIPTION OF THE DRAWINGS
[0032] FIGS. 1a and 1b are isometric and side schematic views,
respectively, of a known patellar tendon graft, not the
invention.
[0033] FIGS. 2a and 2b are isometric and side schematic views,
respectively, of a variation of the graft.
[0034] FIG. 3a is a strength vs. time graph of variations of the
graft with a biodegradable synthetic component and an exemplary
traditional biologic allograft or autograft graft.
[0035] FIG. 3b is a strength vs. time graph of variations of the
graft with a non-biodegradable synthetic component and an exemplary
traditional biologic allograft or autograft graft.
[0036] FIG. 3c is a strength vs. time graph of variations of the
graft with a synthetic component and an exemplary traditional
biologic allograft or autograft graft of tendon mixed with muscle
tissue.
[0037] FIGS. 4a through 7b schematically illustrate a variation of
a method for making the graft. FIGS. 4a, 5a, 6a, and 7a are
isometric views, and FIGS. 4b, 5b, 6b, and 7b are side views of the
respectively numbered isometric views.
[0038] FIG. 8 is a perspective schematic view of a variation of a
method for assembling the graft.
[0039] FIG. 9 is a perspective schematic view of a variation of a
method for assembling the graft.
[0040] FIG. 10 is a cross-sectional view of a variation of the
assembled graft of FIG. 9.
[0041] FIG. 11 is an isometric schematic view of a variation of the
bone plug.
[0042] FIG. 12 is an isometric schematic view of a variation of the
graft.
[0043] FIGS. 13a through 15b schematically illustrate a variation a
method for making the graft. FIGS. 13a, 14a, and 15a are isometric
views, and FIGS. 13b, 14b, and 15b are side views of the
respectively numbered isometric views.
[0044] FIGS. 16 through 19b schematically illustrate a variation of
a method for making the graft. FIGS. 19a and 19b are schematic
isometric and side views, respectively, of the particular variation
of the graft.
[0045] FIGS. 20 through 22 illustrate schematic variations of the
graft.
[0046] FIGS. 23 and 34 schematically illustrate variations of
methods for using variations of the graft with a friction-fit
screw.
[0047] FIGS. 25a through 26b schematically illustrate a variation a
method for making the graft. FIGS. 25a and 26a are isometric views,
and FIGS. 25b and 26b are side views of the respectively numbered
isometric views.
[0048] FIGS. 27 through 29 schematically illustrate a variation a
method for making the graft.
DETAILED DESCRIPTION
[0049] FIGS. 2a and 2b illustrate that a device, such as a
synthetically reinforced orthopedic graft (e.g., an ACL graft), can
have a composite intermingling, interweaving, interstitching,
innerlacing, comingling, blending, merging, or combinations
thereof, of one or more a natural biologic components and one or
more synthetic components.
[0050] The graft can be used for tendon or ligament replacement,
for example, in the knees (e.g., ACL, PCL, MCL, LCL), ankles (e.g.,
lateral ankle ligament), shoulder (e.g., GHL, CAL, CCL, THL), spine
(e.g., spinal ligament), or combinations thereof.
[0051] The biologic component can be a biologic graft, such as a
patellar tendon graft, as shown in FIGS. 1a and 1b, other biologic
graft listed herein (e.g., fascia lata grafts, hamstring grafts,
and quadriceps grafts), or combinations thereof. The biological
component can have soft (e.g., fascia membrane, ligament, tendon,
muscle, or combinations thereof), hard (e.g., bone) tissue, or
combinations thereof. Biologic component can be an allograft,
xenograft, autograft, or combinations thereof.
[0052] The biological components can be near net shape, partial net
shape, assembled, or combinations thereof.
[0053] The near net shape can, for example, be a patellar-tendon
(e.g., bone plug-tendon-bone plug) source graft, such as shown in
FIGS. 1a through 2b. The final part shape or geometry of the near
net shape can be defined by the natural geometry of the original
source of the biological component.
[0054] The partial net shape can, for example, be an Achilles
tendon (soft tissue connected to bone on one end) graft, such as
shown in FIGS. 4a through 7b. The final part shape of geometry of
the partial net shape can be defined by modification to the
original source soft tissue element (tendon, ligament, ECM) of the
biological component.
[0055] The assembled biological component can have a final shape
created by a surgeon or engineers before or during a surgical
procedure by assembling hard (e.g., bone) and soft (e.g., tendon,
ligament, ECM) components into a singular structure of the
biological component, such as shown in FIGS. 8-10. For example, the
assembled biological component can be assembled from bone pieces
(e.g., plugs, wedges, struts, cortical, cancellous, composite of
cortical and cancellous, or combinations thereof), soft tissue
(e.g., semitendinosus, peroneus longus tendon, gracilis tendon,
anterior or anterior tibialis tendon, or combinations thereof),
synthetic component and/or other adhesive element, such as by
sewing two smaller or thinner autografts or allografts together,
for example sewing a first patellar tendon to a second patella
tendon, end to end.
[0056] The synthetic component can be made from a polymer, metal, a
natural material such as collagen, cat gut, silk, HA, cytosan, or
combinations thereof, Can be biodegradable (e.g., hydrolytic or
pyrolytic), or non-biodegradable. The synthetic component can be
one or more yarns, threads (e.g., multifilament or monofilament),
fibers, leaders, wires, cords, or combinations thereof. The
synthetic component can be a thread. The synthetic element can be
inserted through, around, between, inside, or combinations thereof,
the hard and/or soft tissue of the biologic component.
[0057] The synthetic component can be configured to bear tensile
load when the biological component is under a tensile load. The
synthetic components can structurally reinforce the biologic
component, for example, when tensile loads are applied to the
graft.
[0058] The graft can have a first synthetic component having a
first yarn stitched through the tendon. The graft can have a second
synthetic component having a second yarn stitched through a
proximal bone plug and the proximal end of the tendon. The graft
can have a third synthetic component having a third yarn stitched
through a distal bone plug and the distal end of the tendon.
[0059] The first, second, and third yarns can all have the same or
different diameters or combinations thereof. For example, the
second and third yarns can have the same diameter which can be
larger than the diameter of the first yarn.
[0060] The first, second, and third yarns can all be made from the
same or different materials. For example, the second and third
yarns can be made from a non-biodegradable materials, and the first
yarn can be made from a biodegradable material. Any or all of the
yarns can be completely biodegradable or bioabsorbable, or
non-biodegradable or non-bioabsorbable.
[0061] For example, the second and third yarns (and/or the first
yarn) can be multifilament yarns, from about 80 to about 1000
denier, and made from PET, PP, or UHMWPE with a twist, can be
braided, and can be inserted (e.g., sewn) and interwoven (e.g.,
lockstitched) through the bone and tendon.
[0062] Also for example, the first yarn (and/or second and/or third
yarns) can be made from PGA, PLLA, PLA, PDI, PCL, inserted (e.g.,
sewn) and interwoven (e.g., lockstitched) through the tendon, and
can the compliance or amount of stretch until yield can be the same
or less than that of the substrate tissue (e.g., tendon), for
example backstopping the tendon (i.e., providing additional tensile
support for the tendon if the tendon is strained beyond expected
normal recovery strain).
[0063] The second yarn and first yarn can overlap, interweaved or
not, in a transition zone at the proximal end of the tendon. The
third yarn and first yarn can overlap, interweaved or not, in a
transition zone at the distal end of the tendon. When the graft is
under tensile stress, the respective yarns can directly transfer
tensile loads between the yarns in the transition zones or merely
indirectly transfer loads (e.g., the first yarn can transfer a
tensile load to the tendon without directly transferring the load
to the second yarn, and the tendon can then transfer the tensile
load to the second yarn).
[0064] The synthetic component can be intermingled throughout the
biologic component by sewing (e.g., by a lockstitch or chain
stitch), knitting, weaving, braiding, gluing, welding, ultrasonic
welding, or combinations thereof. The synthetic component (e.g.,
yarn) can be inserted through the biologic component. The insertion
can be done by a needle which pierces a substrate (i.e., the
biological component). The synthetic component can transverse the
biologic component non-parallel to the layers and/or surface of the
biological component.
[0065] The graft can have tensile and/or compressive load sharing
between the synthetic and biological components. The strength and
compliance of the graft can be shared by the synthetic element and
the biologic simultaneously. For example, the synthetic component
may not stress shield the biological component and vice versa.
[0066] Most (e.g., greater than about 50%, or greater than about
75%, or greater than 90%) or all of the length of the synthetic
component can be inside of the biological component, for example
protected from abrasion by forces outside of the graft (e.g.,
rubbing against external tissue), and inflammatory or foreign body
reaction by the in vivo environment outside of the biological
component.
[0067] The synthetic component can hold or secure shapes and layers
of the biological component together, for example to create complex
3-D composite shapes from biological components, such as shown in
FIGS. 19a and 19b.
[0068] The synthetic components can partially or completely
traverse the thickness or all or part of the biological component.
The synthetic components can be stronger and/or stiffer than the
biological components. The stitch pattern of the synthetic
components and the intermingled nature of the synthetic with the
biological components composite can allow the yarns to offload
stress from the biological component and compress the biological
component. A crimp interchange can allow the yarn filaments to move
and provide relative compliance to match the biologic or backstop
(retard elongation). A crimp interchange can have the stitch
pattern as a spring, pulled axially. The boundaries of the "cells"
of the crimp interchange can stretch and become two straight lines
(i.e., the springs). The biological component tissue can be inside
the "cells," for example, sharing, matching, and/or self-buffering
the force load between the biological and synthetic components.
[0069] The graft can be from about 0% to about 100% synthetic
component by volume, more narrowly from about 1% to about 20%
synthetic component by volume, more narrowly from about 2% to about
10% synthetic component by volume.
[0070] The synthetic component can be used in only specific regions
of the biologic component, such as only on the medial, or proximal,
or distal, or lateral side of biologic component, or only in the
transition zones and the adjacent hard and soft tissue, or
combinations thereof.
[0071] The load forces applied to the biological component can
smoothly (i.e., non-discretely) transition from the hard tissue to
the soft tissue along the lengths of the transition zones. For
example, the overlapping synthetic components can smoothly transfer
the load between the first yarn and the second yarn in the
transition zone. The first yarn can biodegrade over time (e.g.,
after 4 months) after implantation, for example, resisting tension,
abrasion, and fatigue of the biological component until healing and
re-strengthening of the biological component has substantially
completed post-implant.
[0072] The graft can have a higher fracture toughness, mechanical
strength, tensile strength (e.g., modulus of elasticity, yield, and
failure strengths), shear strength, compression strength, torsion
strength, and fatigue properties (e.g., hysteresis) than the
respective unreinforced biological tissue (e.g., tendon and/or
bone/hard tissue).
[0073] The synthetic component-reinforced hard tissue (e.g., bone)
can have altered anisotropic properties, directional strength,
modulus of elasticity, compliance, or combinations thereof compared
with the respective unreinforced hard tissue. The hard tissue can
be reinforced, for example, with single sewn thread systems (hand
or machine sewn), fabric structures, larger cable like structures,
other synthetic components described here, or combinations thereof.
The synthetic components in the hard tissues can be made from
polymers, metals, other materials disclosed herein, or combinations
thereof.
[0074] FIGS. 3a, 3b, and 3c illustrate strength curves of the graft
variations over time after implantation. The loss of strength and
compliance of a purely biological graft is known after a typical
allograft or autograft is implanted in a patient. Tendons used as a
biological component can lose up to 50% of their strength by the
third month after implantation. The graphs illustrate exemplary
composite mechanics of the present graft compared to a
non-reinforced purely biological implant.
[0075] FIG. 3a is a strength vs. time graph of variations of the
graft with a biodegradable synthetic component and an exemplary
traditional biologic allograft or autograft graft.
[0076] FIG. 3b is a strength vs. time graph of variations of the
graft with a non-biodegradable synthetic component and an exemplary
traditional biologic allograft or autograft graft.
[0077] FIG. 3c is a strength vs. time graph of variations of the
graft with a synthetic component and an exemplary traditional
biologic allograft or autograft graft of tendon mixed with muscle
tissue.
[0078] The graft performance of implanted strength over time can be
have a negative slope (i.e., strength loss over time), positive
slope (i.e., strength increase), or zero or flat slope (i.e., no
strength change over time).
[0079] FIGS. 4a and 4b illustrate an Achilles tendon source tissue
for the biological component. The biological component can have a
bone plug at one end of the component. The tendon can be
substantially trapezoidal with a narrow width at the end near the
bone plug and a wider width at the end opposite the bone plug.
[0080] FIGS. 5a and 5b illustrate that the wider side corners of
the tendon can be folded in opposite directions toward the
longitudinal axis of the tendon, as shown by arrows, and sewn onto
the remainder of the tendon.
[0081] FIGS. 6a and 6b illustrate that the bone-less longitudinal
end of the tendon can be rotated (e.g., flipped), as shown by
arrow, around the longitudinal middle of the tendon and sewn to the
other end of the tendon and/or the bone, for example with
additional first or second yarn, and/or a third yarn. The crease of
the fold can be an attachment pocket between the front length of
the tendon and the back length of the tendon. A polymer ring or
clasp (for example, that can be attached to tethers and/or one or
more endobuttons) can be inserted through and be held by the
attachment pocket. The front length of the tendon and the back
length of the tendon can be left unsewn together along the
pocket.
[0082] FIGS. 7a and 7b illustrate that the bone-less longitudinal
end of the tendon can be rotated (e.g., flipped) again, as shown by
arrow, around the longitudinal middle of the tendon and sewn to the
other end of the tendon and/or the bone, as described in FIGS. 6a
and 6b. A second bone plug can then be attached (e.g., sewn) onto
the bone-less longitudinal end of the tendon with the third
yarn.
[0083] The grafts shown herein can be implanted to a target site at
any point or stage during the methods of making shown herein.
[0084] FIG. 8 illustrates that the graft can have interference
bumps attached to the tendon. For example, the interference bumps
can be sewn (e.g., with the first or second yarn) or adhered to the
tendon. The first and second yarns can be longitudinally
coincidental along the length of the tendon. The interference bumps
can extend away from the tendon.
[0085] The tendon can be assembled from a number of layers of the
same or different types of soft tissue that are sewn with one or
more yarns or otherwise adhered together.
[0086] Multiple biologic components can be laminated or sewn
together with the synthetic components. For example, a first layer
of the graft can be a first biological component from a hamstring,
a second layer of the graft can be a second biological component
from the Achilles tendon, and a third layer of the graft can be a
third biological component from the patellar tendon. The multiple
biological components can have the same or different
characteristics such as sidedness (e.g., rough or smooth), density,
surface area (e.g., via papilla, ridges, holes, wrinkles,
trabecular structure, or combinations thereof), layers of tissue
for cell infiltration, holes for cell infiltration, biologic
mechanical properties (e.g., strong or weak, stiff or elastic),
porosity size and pore density, or combinations thereof.
[0087] The bone plugs can have cylindrical configurations with
lateral slots or channels. The bone plugs can be translated or slid
laterally, as shown by arrows, onto the tendon between the
interference bumps. The bone plugs can then be sewn or adhered to
the tendon (e.g., with the second yarn or third yarn). Excess
length of tendon extending to the terminal ends of the tendon
beyond the bone plug can be cut (e.g., past the interference bump
on the terminal side of the bone plug) from the graft before
implantation. Therefore, the graft length and bone plug location
along the tendon can be adjusted by the surgeon after visualizing
(directly or indirectly, such as through an artheroscope or MRI)
and immediately before implantation, or after sizing by inserting
and then withdrawing the graft and then further adjusting the graft
length or bone plug position.
[0088] Pulling tethers can be attached to the bone plugs and/or the
tendon. The pulling tethers can be various sizes, such as sized for
small bore (e.g., soft tissue repair of the knee or shoulder), or
large bore anchor systems (e.g., knee, hip, ankle, spine). The one
or more pulling tethers can extend from the remainder of the
device. The pulling tethers can be pulled on to translate the
device through bone tunnels during placement of the device at the
target site.
[0089] FIG. 9 illustrates that a terminal end of the tendon can be
folded onto itself and sewed or adhered down upon itself to create
a wider diameter than the remainder of the tendon at a fabricated
interference. The bone plug can have a longitudinal channel or
slot. The diameter of the longitudinal channel can be smaller than
the diameter of the fabricated interference. The bone plug can be
translated or slid, as shown by arrow, over the opposite end of the
tendon from the fabricated interference.
[0090] FIG. 10 illustrates that the bone plug can be pushed onto
the fabricated interference. The fabricated interference can have a
fold crease from folding the tendon upon itself. A locking suture
can be sewn tightly into or through the fabricated interference and
through the fold crease, for example, to hold the fabricated
interference in place. The bone plug can friction fit and/or
interference fit on the fabricated interference and/or otherwise
sewn or adhered to the tendon.
[0091] A second bone plug can be slid onto the tendon. A second
fabricated interference can then be formed and the second bone plug
can friction fit and/or interference fit on the second fabricated
interference and/or otherwise sewn or adhered to the tendon.
[0092] FIGS. 11 and 12 illustrate that the bone plugs can have
first, second, and/or third yarns through the bone plugs in one or
more directions. For example, the first yarn can intersect the
second yarn crossing along radial coordinates in the bone plug as
shown in FIG. 11. The first yarn can intersect the second yarn
crossing perpendicularly or at a non-perpendicular angle along
orthogonal coordinates in the bone plug as shown in FIG. 12. The
first and second yarns can have different strengths, for example
resulting in differing additional strength in different directions
along the bone plug.
[0093] FIGS. 13a and 13b illustrate that multiple source biological
components similar to the component shown in FIGS. 4a and 4b (e.g.,
Achilles tendon-sourced components) can be placed on top of each
other in longitudinally opposite orientation. Similar to the method
shown in FIGS. 5a and 5b, the wider side corners of the tendons can
be folded toward the longitudinal axis of the tendon, as shown by
arrows, but in the same direction, partially or completely
enveloping, encapsulating, or encircling the opposite biological
component, and sewn onto the remainder of the tendon and/or to the
tendon and/or bone of the opposite biological component, as shown
in FIGS. 14a and 14b. The first yard can extend parallel to the
longitudinal axis of the graft. The second (or first) yarn can
zig-zag back and forth across the graft at about 45.degree. and
about 135.degree. angles to the longitudinal axis, crossing the
first yarn that extends parallel to the longitudinal axis, further
securing the first tendon to the second tendon.
[0094] FIGS. 15a and 15b illustrate that the graft can be wrapped
in another soft tissue component, such as tendon or muscle, or
co-joined biologics such as tendon with muscle and/or ligament with
muscle. The wrapping can partially or completely envelope,
encapsulate, or encircle the soft and/or hard tissue of the
remainder of the graft and can be attached to the remainder of the
graft by adhering or sewing, for example with the third (and/or
first and/or second) yarn zig-zagging at about 30.degree. and about
150.degree. angles to the longitudinal axis.
[0095] FIG. 16 illustrates a biological component similar to the
component shown in FIGS. 4a and 4b (e.g., Achilles tendon-sourced
components) that can have a first yarn sewn through the tendon. The
bone-less longitudinal end of the tendon can be rotated (e.g.,
flipped), as shown by arrow, around the longitudinal mid-line of
the tendon, as shown in FIG. 17. The free flap of the tendon can be
sewn to the other end of the tendon and/or the bone, for example
with additional first or second yarn.
[0096] FIG. 18 illustrates that the method shown in FIGS. 16 and 17
can be performed on two biological components/grafts. The
biological components/grafts can be oriented longitudinally
opposite to each other and then brought into contact with each
other into an assembly as shown by arrow.
[0097] FIGS. 19a and 19b illustrates that the assembly of FIG. 18
can then be secured together with adhesive and/or second (and
third, if desired) yarn stitched through the tendons of both
biological components. The resulting graft can have four layers of
tendons (i.e., each of two biological component tendons folded over
onto itself).
[0098] Other tendons in the body that can be soft tissue, for
example as layers and sewn together, include the iliofemoral
ligament, hamstring, sartorius, thoracolumbar facia (thin wide
sheets of tendon), or combinations thereof.
[0099] The assembled biological devices can have the bone anchors
pre-attached or attached and installed during surgery. The bone
anchors can lock on to the remainder of the device by an
interference fit of be sutured in place. The bone anchors can be
external to the soft tissue or embedded inside the soft tissue
element.
[0100] The biological tissue component or element can be 100% soft
tissue or have a single or more than one hard tissue (e.g., bone)
element. The hard tissue elements can be harvested pre-attached or
post sewn in place.
[0101] The reinforced graft can have a secondary tissue source,
thereby being a Hybrid Biologic Device (HBD), as shown in FIGS. 13a
through 15b and 18 through 19b. The HBD can source biological
components from tissue that are complimentary in characteristics,
such as a higher strength tissue combined with a tissue with faster
healing kinetics. For example, less dense by weight (g/cc) tissue,
more open (i.e., porous) tissue, and less inflammatory tissue can
be used with similar tissue and/or with tissue with more strength
but a higher density and less porous. HBD tissue can include
combinations of muscle tissue, peritoneum, rumen, stomach, urinary
bladder, liver, human dermis, fetal bovine dermis (e.g., as less
strong but faster healing) with other similar tissue or with higher
strength biological source tissue mentioned elsewhere herein. The
HBD could also be a combination of textile or film structure. For
example a weave of warp knitted structure or degrading (e.g.,
biodegradable) or non-degrading (e.g., non-biodegradable) material.
The textile or film can be secured to a biologic component with
sewing as illustrated herein.
[0102] FIG. 20 illustrates that the graft can have a tether sewn
into the graft and extending from the terminal end of the remainder
of the graft. The tethers can be used to pull the graft into a
target site, such as a bone tunnel. The tether can extend from the
radial center or radial edge of the graft.
[0103] The device can have one or more endobutton fixation
elements. For example, the endobuttons can attach to the tethers
and rest, press, or be separately fixed (e.g., with bone screws)
against the outer cortical surface of the bone on the outside of
the bone tunnels. The endobuttons can be attached to the tethers
like a The endobuttons can be wider than the bone tunnel. The
endobutton can fix the device at the target site by preventing or
minimizing translation away from the endobutton.
[0104] FIG. 21 illustrates that the tether can extend from the
radially outer surface of the graft at one or more points, such as
encircling the graft and attaching by adhering to or weaving
through along part or all of the outer circumference. The tether
can be sewn deeper into the graft.
[0105] FIG. 22 illustrates that one or both of the opposite
longitudinal ends of the graft can have supplemental
reinforcements, such as meshes or screens. The supplemental
reinforcements can have additional yarn, higher stitch densities,
larger diameter yarn, stronger material yarn, or combinations
thereof, than the remainder of the graft. For example, tethers can
be attached to the supplemental reinforcements. A static or
expanding screw can be inserted into or radially adjacent to the
length of the supplemental reinforcement to friction fit the graft
into the target site.
[0106] The sewn reinforcement, such as the supplemental
reinforcement or any of the synthetic components, can bolster
proximal and distal implant anchoring zones in the graft. A soft
tissue implant can be developed to behave and be anchored like a
bone tendon bone. The supplemental reinforcement can increase the
stitch density at the implant end sections, for example by adding
additional structures to the biologic component such as open pore
textile structures and tethers (e.g., lines, cords, sutures, or
combinations thereof).
[0107] FIG. 23 illustrates that the graft can have pocket collars
attached to one or both of the opposite longitudinal ends of the
graft. The pocket collars can be made from macro pore fabric, any
other material disclosed herein, or combinations thereof. The
pocket collars can be attached to the remainder of the graft, for
example by stitching the collar to the remainder of the graft with
the third (and/or first and/or second) yarn. The pocket collars can
have hollow pockets extending laterally away from the graft. When
the graft is at the target site, one or more friction fit screws
can be inserted into the pockets, as shown by arrow, to friction
fit the graft into the target site.
[0108] FIG. 24 illustrates that the graft can have a hollow lumen
through the entire length of graft or only at one or both terminal
ends. The lumen can be radially central and collinear with the
longitudinal axis or radially offset. A guidewire can be deployed
through the lumen, for example, to deliver the graft to the target
site. The lumen can also form a pocket to receive a screw. A static
or radially expanding screw, such as a bone screw, can be inserted
into the lumen to expand the graft, as shown by arrows, and
friction fit the graft into the target site.
[0109] The graft shown in FIG. 24 can be made by rolling any of the
flat variations described herein. For example, the bone plug ends
can be shaped to accept a smaller screw. The bone plug can be cut
into four quarters. The screw can be pushed through the middle of
the bone plug quarters causing the plug quarters to expand. The
bone plug can be tapered proximal to distal. As the screw is
screwed in, the screw can push the bone plug deeper radially into
the bone tunnel wall of the target site.
[0110] FIGS. 25a and 25b illustrate a biological component similar
to the component shown in FIGS. 4a and 4b (e.g., Achilles
tendon-sourced components) that can have a first tendon and a
second tendon directly in contact with each other, approximately
the same size and shape, and aligned with each other.
[0111] FIGS. 26a and 26b illustrate that the wider side corners of
the first and second tendons can be folded in opposite directions
toward the longitudinal axis of the tendon, as shown by arrows, and
sewn onto the remainder of the tendons.
[0112] FIG. 27 illustrates that the second yarn can, for example,
secure any additional soft tissue layers together. The first yarn
can, for example, supplement the axial strength of the graft, for
example during the healing stage. The first yarn can form a
lockstitch with the second yarn. The top and bottom yarns in the
lockstitch can have the same or different materials, diameters,
filament quantity (e.g., monofilament or multifilament),
biodegradability (e.g., capable of biodegrading at all and the rate
of degradation), or combinations thereof.
[0113] The graft can have a float zone where the second yarn is
absent. The float zone can be an area where the stitch of the
second yarn (or respective yarn of the particular float zone) skips
an additional distance and "floats," for example outside of the
biological component, to a location outside of the float zone where
the regular stitch pattern resumes. The float zone can have a
reduced stitch density relative to the non-float zones. The float
zones can have reduced stiffness and higher flexibility than the
remainder of the device.
[0114] FIG. 28 illustrates that the graft can be rolled, as shown
by arrows, into a cylinder.
[0115] FIG. 29 illustrates that the graft can be folded over, as
shown by arrow, around the longitudinal mid-point.
[0116] Yarns or threads can be sewn in strength lines for axial
strength.
[0117] Threads can be sewn in, for example, straight, zig zag, or
saw tooth patterns for securing layers together.
[0118] When systems of biologic components are sewn together, the
larger diameter filaments can be hidden inside the final part. For
example two layers of biologic material can be sewn together, 4/0
suture top surface, 2/0 bottom surface. The structure can be rolled
so the 2/0 suture are oriented toward the inside of the cylindrical
roll. (4/0 and 2/0 refer to exemplary USP suture sizes.)
[0119] Larger and/or high density yarns than the rest of the yarns
can be used in some locations along the surface of the graft, for
example, to increase the roughness of the surface texture and
friction between the graft and surrounding tissue, and anchor
(e.g., friction fit screw) engagement against the graft.
[0120] The synthetic components can have a stitch density, stitch
length, stitch pattern and filament size.
[0121] Exemplary combinations of elements and characteristics for
non-limiting variations of the graft include:
[0122] The graft can have a hamstring tendon (such as FIGS. 4a and
4b without a bone plug), with no bone plug as the biological
component or orthobiologic structure sewn with a 0 UHMWPE braided
suture (i.e., yarn). The graft can have six straight sew lines of
the suture using a lockstitch pattern white thread with a 5 mm
stitch length. The suture can penetrate the hamstring tendon. The
graft can have two hamstring tendons. The two tendons combined
folded in half (e.g., stacked) and then sewn together using a 2/0
black UHMWPE braided suture in either straight lines of diamond
pattern. The graft can have a 5 mm stitch length lock stitch
[0123] The graft can have soft tissue tendonous facia with no bone
plug, similar to FIGS. 27 through 29 as the biological component or
orthobiologic structure sewn with a first yarn of 0 UHMWPE braided
suture. A second yarn threads can be 0 UHMWPE and be braided
sutures sewn into the high stress regions, such as transitions
zones. The graft can have 12 straight sew lines using a lock stitch
pattern for the first yarn with a 5 mm stitch length. The suture
can penetrate the facia sheet. (Wider, thinner soft tissue can have
12 stitch lines spaced further apart than above.) The sheet can
then be rolled, folded in half (i.e., stacked) and then sewn
together using a 2/0 black UHMWPE braided suture in either straight
lines or a diamond pattern using a 5 mm stitch length lock stitch
or a surgeon whip stitch.
[0124] The graft can have soft tissue Achilles tendon with a bone
plug, such as FIGS. 4a and 4b, the biological component or
orthobiologic structure sewn with a 0 UHMWPE braided suture as the
first yarn. The graft can have 12 sew lines (e.g., fanning shape,
narrow at bone tendon interface) using a lock stitch pattern white
thread with a 5 mm stitch length. The suture can penetrate the
tendon. The tendon can be folded in thirds (stacked) and then sewn
together using a 2/0 black UHMWPE braided suture in either straight
lines of diamond pattern with a 5 mm stitch length lock stitch. The
tendon can then be folded in half length-wise and then sewn
together using a 2/0 black UHMWPE braided suture in either straight
lines of diamond pattern with a 5 mm stitch length lock stitch.
[0125] The biological component or orthobiologic structure can be
two Achilles tendons with bone plugs as sewn with a 2/0 UHMWPE
braided suture as the first yarn. The graft can have 12 sew lines
(fanning shape, narrow at bone tendon interface) using a lock
stitch pattern white thread with a 5 mm stitch length for the first
yarn. The suture can penetrate the tendon. Two of these structures
can be made and combined to make final graft. The tendons can be
folded in half and then sewn together using a 2/0 black UHMWPE
braided suture in either straight lines of diamond pattern using a
5 mm stitch length lock stitch.
[0126] Any of the above devices can have fabric attached to the
ends of the device, similar to that shown in FIG. 23. The fabric
can be a pre-shaped warp knitted mesh tube made from any of the
materials herein, such as Polypropylene or UHMWPE polymers. Warp
knit fabric can have an weight density per coverage area of about
70 g/cm{circumflex over ( )}2 and an average pore size of about 2
mm.
[0127] Any or all elements of the synthetic components and/or other
devices or apparatuses described herein (including other
non-biological elements of the graft) can be made from, for
example, a single or multiple stainless steel alloys, nickel
titanium alloys (e.g., Nitinol), cobalt-chrome alloys (e.g.,
ELGILOY.RTM. from Elgin Specialty Metals, Elgin, Ill.;
CONICHROME.RTM. from Carpenter Metals Corp., Wyomissing, Pa.),
nickel-cobalt alloys (e.g., MP35N.RTM. from Magellan Industrial
Trading Company, Inc., Westport, Conn.), molybdenum alloys (e.g.,
molybdenum TZM alloy, for example as disclosed in International
Pub. No. WO 03/082363 A2, published 9 Oct. 2003, which is herein
incorporated by reference in its entirety), tungsten-rhenium
alloys, for example, as disclosed in International Pub. No. WO
03/082363, polymers such as polyethylene teraphathalate (PET),
polyester (e.g., DACRON.RTM. from E. I. Du Pont de Nemours and
Company, Wilmington, Del.), poly ester amide (PEA), polypropylene,
aromatic polyesters, such as liquid crystal polymers (e.g.,
Vectran, from Kuraray Co., Ltd., Tokyo, Japan), ultra high
molecular weight polyethylene (i.e., extended chain, high-modulus
or high-performance polyethylene) fiber and/or yarn (e.g.,
SPECTRA.RTM. Fiber and SPECTRA.RTM. Guard, from Honeywell
International, Inc., Morris Township, N.J., or DYNEEMA.RTM. from
Royal DSM N.V., Heerlen, the Netherlands), polytetrafluoroethylene
(PTFE), expanded PTFE (ePTFE), polyether ketone (PEK), polyether
ether ketone (PEEK), poly ether ketone ketone (PEKK) (also poly
aryl ether ketone ketone), nylon, polyether-block co-polyamide
polymers (e.g., PEBAX.RTM. from ATOFINA, Paris, France), aliphatic
polyether polyurethanes (e.g., TECOFLEX.RTM. from Thermedics
Polymer Products, Wilmington, Mass.), polyvinyl chloride (PVC),
polyurethane, thermoplastic, fluorinated ethylene propylene (FEP),
absorbable or resorbable polymers such as polyglycolic acid (PGA),
poly-L-glycolic acid (PLGA), polylactic acid (PLA), poly-L-lactic
acid (PLLA), polycaprolactone (PCL), polyethyl acrylate (PEA),
polydioxanone (PDS), and pseudo-polyamino tyrosine-based acids,
extruded collagen, silicone, zinc, echogenic, radioactive,
radiopaque materials, any of the other materials listed herein or
combinations thereof. Examples of radiopaque materials are barium
sulfate, zinc oxide, titanium, stainless steel, nickel-titanium
alloys, tantalum and gold.
[0128] The synthetic components of the device can be made from
substantially 100% PEEK, substantially 100% titanium or titanium
alloy, or combinations thereof.
[0129] The synthetic (and biological) elements described herein can
be made (at least) in part from a biomaterial (e.g., cadaver
tissue, collagen, allograft, autograft, xenograft, bone cement,
morselized bone, osteogenic powder, beads of bone).
[0130] Any or all elements of the device and/or other devices or
apparatuses described herein, can be, have, and/or be completely or
partially coated with agents for cell ingrowth.
[0131] The device and/or elements of the device and/or other
devices or apparatuses described herein can be filled, coated,
layered and/or otherwise made with and/or from cements, fillers,
and/or glues known to one having ordinary skill in the art and/or a
therapeutic and/or diagnostic agent. Any of these cements and/or
fillers and/or glues can be osteogenic and osteoinductive growth
factors.
[0132] Examples of such cements and/or fillers includes bone chips,
demineralized bone matrix (DBM), calcium sulfate, coralline
hydroxyapatite, biocoral, tricalcium phosphate, calcium phosphate,
polymethyl methacrylate (PMMA), biodegradable ceramics, bioactive
glasses, hyaluronic acid, lactoferrin, bone morphogenic proteins
(BMPs) such as recombinant human bone morphogenetic proteins
(rhBMPs), other materials described herein, or combinations
thereof.
[0133] The agents within these matrices can include any agent
disclosed herein or combinations thereof, including radioactive
materials; radiopaque materials; cytogenic agents; cytotoxic
agents; cytostatic agents; thrombogenic agents, for example
polyurethane, cellulose acetate polymer mixed with bismuth
trioxide, and ethylene vinyl alcohol; lubricious, hydrophilic
materials; phosphor cholene; anti-inflammatory agents, for example
non-steroidal anti-inflammatories (NSAIDs) such as cyclooxygenase-1
(COX-1) inhibitors (e.g., acetylsalicylic acid, for example
ASPIRIN.RTM. from Bayer AG, Leverkusen, Germany; ibuprofen, for
example ADVIL.RTM. from Wyeth, Collegeville, Pa.; indomethacin;
mefenamic acid), COX-2 inhibitors (e.g., VIOXX.RTM. from Merck
& Co., Inc., Whitehouse Station, N.J.; CELEBREX.RTM. from
Pharmacia Corp., Peapack, N.J.; COX-1 inhibitors);
immunosuppressive agents, for example Sirolimus (RAPAMUNE.RTM.,
from Wyeth, Collegeville, Pa.), or matrix metalloproteinase (MMP)
inhibitors (e.g., tetracycline and tetracycline derivatives) that
act early within the pathways of an inflammatory response. Examples
of other agents are provided in Walton et al, Inhibition of
Prostoglandin E2 Synthesis in Abdominal Aortic Aneurysms,
Circulation, Jul. 6, 1999, 48-54; Tambiah et al, Provocation of
Experimental Aortic Inflammation Mediators and Chlamydia
Pneumoniae, Brit. J. Surgery 88 (7), 935-940; Franklin et al,
Uptake of Tetracycline by Aortic Aneurysm Wall and Its Effect on
Inflammation and Proteolysis, Brit. J. Surgery 86 (6), 771-775; Xu
et al, Spl Increases Expression of Cyclooxygenase-2 in Hypoxic
Vascular Endothelium, J. Biological Chemistry 275 (32) 24583-24589;
and Pyo et al, Targeted Gene Disruption of Matrix
Metalloproteinase-9 (Gelatinase B) Suppresses Development of
Experimental Abdominal Aortic Aneurysms, J. Clinical Investigation
105 (11), 1641-1649 which are all incorporated by reference in
their entireties.
[0134] Bone plugs as shown herein can be bone pieces, wedges,
struts, cortical bone, cancellous bone, composites of cortical and
cancellous bone, or combinations thereof.
[0135] Any elements described herein as singular can be pluralized
(i.e., anything described as "one" can be more than one). Any
species element of a genus element can have the characteristics or
elements of any other species element of that genus. (e.g.,
"Tendon" is used as an exemplary soft tissue throughout the
disclosure, but can be any soft tissue or combinations thereof.
"Yarn" is used as an exemplary synthetic component throughout the
disclosure but can be any synthetic component or combinations
thereof.) The above-described configurations, elements or complete
assemblies and methods and their elements for carrying out the
invention, and variations of aspects of the invention can be
combined and modified with each other in any combination.
* * * * *